In recent years, dendritic macromolecules have been found to have increasing applications in biotechnology and pharmaceutical applications on the basis of their unique properties and structure, and subsequently, function. Dendritic macromolecules are a special class of polymers with densely branched structures that are characterized by higher concentrations of functional groups per unit of molecular volume than ordinary polymers. There are three subclasses of dendritic macromolecules (Frechet and Tomalia “Dendrimers and other Dendritic Polymers”): random hyperbranched polymers; dendrigraft polymers and dendrimers (which include dendrons), classified on the basis of the relative degree of structural control present in each of the dendritic architectures. Generally, a dendritic macromolecule includes at least two layers or generations of building units and all contain one or more branches originating from a core molecule.
In particular, peptide-based dendritic molecules, such as those based on polylysine FIG. 1, have been developed as promising vaccine, antiviral and antibacterial candidates. A specific architecture of lysine and lysine analogue dendrimers has been described by Denkewalter in U.S. Pat. No. 4,289,872. This patent describes branched compounds essentially of identical lysine-like trifunctional units.
Denkewalter's methodology has the advantage that a plurality of amide linkages are provided to connect the trifunctional units so that the final dendrimeric moiety tends to be biocompatible and locally protein-like. However the dendrimeric moiety thus provided comprises multiple substantially equivalent outer terminal reactable groups (for example amine groups) as the point of attachment for functional moieties and the following adverse consequences arise:                If a further reagent (e.g. a biological effector molecule) is used to react with the outer terminal reactable groups of the dendrimer moiety in such a way that some of the outer terminal reactable groups remain unreacted, there is a statistical spread of reaction products (i.e. monodispersity in the dendrimer is lost in the dendrimer reaction product).        If a combination of reagents is used to react with the outer terminal reactable groups of the dendrimer moiety there is a statistical spread of reaction products and monodispersity is lost. This situation is described by Newkome et, al. (Combinational Chemistry) Vol 61, No 4 1998/99 “Dendrimer Construction and Macromolecular Property Modification Via Combinational Methods” (p 244) in the following terms: “There is an uncontrolled radial monomer juxtaposition while generational functional group control is retained”.        
Thus whilst the generational character in the dendrimer is maintained, and whilst the amide linkages are advantageous in the provision of biocompatibility, the inability to provide radial (i.e. surface decoration) monodispersity is a significant disadvantage.
In U.S. Pat. No. 5,229,490 and WO 9011778, Tam teaches that dendritic core molecules of 2 or 3 generations of lysine may be constructed using solid phase peptide synthesis and making use of orthogonally protected lysine at the final step of the process, to provide a composition that has a surface topology of (PG1PG2)4. In particular, Tam describes a dendritic polymer bearing multiple B- and T-epitopes, wherein the B- and T-epitopes are arranged as couplets (B-epitope T-epitope) on the surface building unit. The process of solid phase peptide synthesis provides no opportunity for purification until after the final iteration of the synthesis. Materials provided by such a method are often mixtures wherein the target component is contaminated by the components which are of amino acid deletion products.
The preparation of dendritic macromolecules with a homogenous surface comprised of only a single type of functional moiety is now considered to be routine. Furthermore, Tam and others provide teaching for the construction of dendritic macromolecules in which a core or macromolecule has a homogenous surface stoichiometry that is 1:1 for two functional moieties A and B. Furthermore the topology of the two functional moieties is specified as homogenous at the level of (AB) couplets; that is each of the surface building units has two functional moieties A and B attached to the same surface building unit (as for FIG. 3.5).
One key determinant of a dendritic macromolecule's efficacy in any given application is the nature of the macromolecule surface. This application describes macromolecule topological isomers using a hierarchy of descriptive terms which serve to elucidate the way functional moieties, surface building units and building units are interconnected.
It is, accordingly, an object of the present invention to overcome or at least alleviate one or more of the difficulties and deficiencies related to the prior art.
It will be understood that the present invention disclosed and defined in this specification extends to all alternative combinations of two or more of the individual features mentioned or evident from the text or drawings. All of these different combinations constitute various alternative aspects of the present invention.
Reference to any prior art in the specification is not, and should not be taken as, an acknowledgment or any form of suggestion that this prior art forms part of the common general knowledge in Australia or any other jurisdiction or that this prior art could reasonably be expected to be ascertained, understood and regarded as relevant by a person skilled in the art.